Innovations at Interphex 2023 - 15

system performance than discrete sampling. " Ultimately,
continuous monitoring will provide a better gauge on the
level of potential contamination that a water system could
be under. Implementing technologies like real-time testing
of TOC and conductivity, at-line evaluation of endotoxin
with microfluidic technology (see previous section), or
bioburden with rapid microbial methods (see previous
section) will be key to detect contamination before water
enters upstream production processes. These monitoring
approaches are ultimately decreasing the time to results
and optimizing overall uptime of production.
The Sievers M500 and Real-Time Release Testing validation
support from the Sievers team enable pharmaceutical
manufacturers to successfully and compliantly implement
RTRT into their facilities. With the adoption of any new
instrument to a facility comes validation, and for the
implementation of RTRT with process analytical technology,
process validation is key. There are inherent risks associated
with the transition from traditional lab-based testing to
online release testing, and those include having a singular
instrument monitoring an entire facility, or an entire loop
of water. Additional testing would include performing
a risk assessment to assess which points of use might be
most critical to the process and product. Once identified, a
company must then understand how that criticality affects
the cleanliness of those points of use. This represents a
singular example of a process validation step, and there is
more associated with the overall process validation. With
validation support from the Sievers Instruments team,
companies feel confident about adopting compliant realtime
testing or monitoring strategies to enhance their
contamination control portfolio.
4. Continuous monitoring for cleaning validation
Cleaning validation samples are frequently tested to ensure
there is no residual contamination on equipment used in
the production process. TOC and conductivity provide
a comprehensive view of chemical contamination from
product carry-over, however often companies are still
analyzing cleaning validation samples in the lab, delaying
equipment release back into production. Lab analysis of
TOC and conductivity also has the potential for introducing
human error when isolating samples.
Online TOC and conductivity monitoring with Sievers M9
Analyzers for cleaning validation enables real-time results
related to equipment cleanliness, enabling companies to
confidently release equipment into production, optimize
uptime, remove delays due to QC workflow, and ultimately
reduce any human error that may be associated with
isolating samples. This enhances their contamination
control strategies as they are able to trend and control in
real time and make decisions on results in real time.
Testing for endotoxin and bioburden are an important part
of risk reduction for cleaning validation programs, as Gramnegative
bacteria can still be present on equipment even
after cleaning or sanitization. However these traditional
testing methods need to be easier and faster to have
utility as at-line or process monitoring tools for cleaning
validation. Now, with Sievers centripetal microfluidics for
BET (see previous section) and RMMs for bioburden (see
previous section), pharmaceutical manufacturers are able
to reduce risks related to equipment contamination using
instrumentation that is simple to use and yields faster
results. Paired with online cleaning validation using Sievers
TOC and conductivity analyzers, manufacturers have a
comprehensive understanding of their cleaning processes
and the ability to make quick decisions to maximize
equipment uptime and production.
Conclusion
Developing a contamination control strategy with
endotoxin, bioburden, TOC, and conductivity testing can
allow for continuous monitoring to optimize uptime and
identify contamination earlier in the process. Innovative
technologies that
test for these parameters align with
the guidelines from Annex 1 to enable better process
understanding and control, and to minimize the risk
of contamination. Sievers Instruments for continuous
monitoring and rapid monitoring make it simpler and faster
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Innovations at Interphex 2023

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